Most research on cell death focused on apoptosis known as programmed cell death (PCD), and as the enzyme caspase was discovered, many pharmaceutical companies continued to develop drugs using caspase inhibitor for the past 10 years. However, up to now, almost no drugs were approved by the FDA. This is because apoptosis, which refers to cell death occurring in physiological circumstances, is likely to be caused by defense mechanism to retain homeostasis in the body. In contrast, necrosis, which refers to cell death occurring in pathologic circumstances, involves inflammation response in almost all cases. Recent research indicated that diseases caused by necrosis are representatively ischemic (for example, myocardial infarction, stroke, renal infraction), neurodegenerative, and inflammatory diseases (Cell Death and Differentiation (2012) 19, 75-86).
Before the 2000s, cell death was recognized as coming into apoptosis and necrosis. Apoptosis is a representative example of regulated cell death, and necrosis is a representative example of non-regulated cell death. However, recently, a form of cell death, which is different from apoptosis, and also shows morphological characteristics of necrosis, while being regulated by specific proteins, is defined as necroptosis which fuses necrosis and apoptosis. Necroptosis, which refers to programmed necrosis, shows unique characteristics of following programmed cell death mechanism similar to apoptosis, different from necrosis disorderly occurring (Necroptosis: a specialized pathway of programmed necrosis; Cell, Volume 135, Issue 7).
Necroptosis is a non-regulated accidental death form in pathologic circumstances, and its mechanism, molecular target, and signal transduction system have not been studied. Thus, no suitable therapeutic agents for necroptosis diseases have been reported, although it is very urgent to discover and develop substances inhibiting necroptosis, to treat diseases caused by necroptosis and reveal its biological and pathological causes.
Necroptosis diseases, which occur by drugs widely prescribed and used, include drug-induced skin diseases occurring by administration of a substance or drug in an excessive amount or in a wrong manner, or an accurate substance or drug used in an appropriate manner. These diseases are known as incurable diseases since causes thereof are hard to find and no suitable therapeutic agents are developed. Particularly, according to the Korean Society for Pharmacoepidemiology and Risk Management, it is known that about 1,700 distributed pharmaceuticals induce drug-induced skin diseases, representatively, Stevens-Johnson syndrome or toxic epidermal necrolysis. Thus, it is very urgent to develop a novel therapeutic agent and method of preventing or treating these diseases.